Following infection with retroviruses, a DNA copy of the viral RNA genome is synthesized in a reaction catalyzed by reverse transcriptase. One or two copies of viral DNA is subsequently integrated into the chromosome of the infected cell. If embryos or cells of the reproductive tract are the target of retrovirus infection, a copy of the viral DNA can be inserted into the germline and be transmitted vertically within a given species. All vertebrates examined to date carry endogenous retroviral sequences. The human genome contains 35 to 50 copies per haploid mass of DNA. These copies are equally divided between full-length (8.8 kb) retroviral structures with LTR, gag, pol and env domains and a truncated class (approximately 4.1 kb in size) containing only gag and pol sequences. Detailed analyses of several human retroviral segments indicate that each contain deletions, stop codons, and frame shifts which render them defective as viruses. On the other hand, long open reading frames abound (pol = 1881 bp; env = 1284 bp). The human endogenous retroviral sequences we have examined possesses two unique structural features that distinguish them from other related retroviral segments: a primer binding site for tRNA-Glu, and a characteristic env gene. Cross-species, high stringency hybridization analyses have shown that the tRNA-Glu class of retroviruses with their distinguishing env gene are present in all primates above old world monkeys. The number of primary germline insertions of retroviral genomes in human chromosomal DNA is far less than would be suggested by the 35 to 50 copies currently detected, suggesting that amplification of large DNA segments involving both viral and cellular sequences has occurred. We have accumulated data which conclusively demonstrates that such amplification has occurred subsequent to the integration of the tRNA-Glu family of retroviruses into the primate germline. Experiments utilizing somatic cell hybrids indicate that the amplified retroviral/flanking cell DNA units have been dispersed to multiple chromosomes.